DNA sequence that increases odorant receptor representation in the olfactory system

Abstract

A genetically modified vertebrate is provided that has an enhanced sense due to an over representation of a predetermined odorant receptor. The vertebrate is genetically modified by introduction of DNA that comprises at least four sequential repeats of a sequence whose primary structure is at least 90% homologous with ACATAACTTTTTAATGAGTCT (SEQ ID NO: 1). The DNA causes a nearby odorant receptor coding sequence to be over represented in a singular gene choice fashion relative to a corresponding vertebrate that lacks the DNA.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and is a continuation of U.S. patent application Ser. No. 15 / 749,007 (filed Jan. 30, 2018) which is U.S. national stage filing under 35 U.S.C. 371 of PCT / US16 / 45338 (filed Aug. 3, 2016) which claims priority to U.S. Patent Application 62 / 200,312 (filed Aug. 3, 2015) and 62 / 312,068 (filed Mar. 23, 2016) the entirety of which are incorporated herein by reference.STATEMENT OF FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant number GM088114-01A1 awarded by the National Institute of Health and grant number MD007599 awarded by the National Institute on Minority Health and Health Disparities. The government has certain rights in the invention.REFERENCE TO A SEQUENCE LISTING[0003]This application contains a Sequence Listing in computer readable form. The computer readable form is incorporated herein by reference.BACKGROUND OF THE INVENTION[0004]The sub...

AI Technical Summary

Benefits of technology

The patent describes a method for genetically modifying non-human vertebrates to have an enhanced sense of smell. This is achieved by inserting DNA into the genome of the vertebrate that contains a sequence that is at least 90% homologous with a specific odorant receptor. The DNA causes an increase in the expression of the odorant receptor, resulting in a main olfactory epithelium that contains multiple olfactory sensory neurons that express the predetermined odorant receptor. The genetically modified vertebrate can also be used for high-throughput screening to identify odorant ligands that bind to the predetermined odorant receptor.

Problems solved by technology

Currently, animals such as dogs, bees and rats are deployed to help humans with scent detection tasks, but their use is expensive since they require long-term training.

There has been limited success in odor profiling ORs expressed in heterologous cells in vitro.

Part of this limitation is due to the inability of OR proteins to traffic to the plasma membrane.

In addition, given the biological properties of the olfactory system many in vitro characterized OR alleles may not be functional in an in vivo setting.

The major drawback, though, has been the ability to rapidly contrast how odors presented in liquid phase (in vitro) correspond to odors presented to the OR in vapor phase within their mucosal environment (in vivo).

In addition, the study of both OR gene choice and OR coding in vivo is hampered by the low representation of a given OR, i.e. only ˜0.1% on average of the total neuronal population in a wild type mouse.

Unfortunately, no suitable in vivo approach is known.

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